Obesity has rapidly become a serious health problem in the United States, with recent reports estimating that nearly one half of the adult population in the US can be classified as overweight or obese**. While much of the research aimed at understanding the genetic and molecular regulation of energy homeostasis has focused on centers in the hypothalamus, it is clear that other brain regions are involved in the regulation of feeding. Evidence suggests that endogenous reward pathways, including the mesolimbic dopamine system play a role in the regulation of feeding and body weight. However, it is not clear how the mesolimbic dopamine system and feeding status interact with and regulate each other. The experiments in this proposal will utilize electrophysiology to examine how the activity of dopamine neurons in the ventral tegmental area (VTA) is modulated by feeding and feeding-related parameters. Leptin and insulin mediate some of their effects on energy homeostasis through their actions in the hypothalamus, but leptin and insulin are also able to modulate feeding related alterations in the mesolimbic dopamine system. However, the molecular mechanisms underlying the effects of leptin and insulin on the reward systems involved in feeding behavior have not been identified. It has also been suggested that the mesolimbic dopamine system may be involved in the intake of palatable foods such as those high in fat or sugar. However, the mechanisms underlying the interactions between reward systems and the intake of palatable foods have not been identified. Thus, the experiments in this specific aim will use electrophysiology to determine the effects of leptin, insulin, and the ingestion of palatable foods on the activity of VTA dopamine neurons. These studies will provide valuable information on the interactions between feeding state and the activity of the mesolimbic dopamine system, and may provide potential targets for the prevention and treatment of obesity.